Sorafenib Triggers Antiproliferative and Pro-Apoptotic Signals in Human Esophageal Adenocarcinoma Cells

• Published in: Digestive diseases and sciences Vol. 53; no. 12; pp. 3055 - 3064
• Main Authors: Delgado, Jorge-Shmuel, Mustafi, Reba, Yee, Jason, Cerda, Sonia, Chumsangsri, Anusara, Dougherty, Urszula, Lichtenstein, Lev, Fichera, Alessandro, Bissonnette, Marc
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2008; Springer; Springer Nature B.V
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzenesulfonates - pharmacology; Biochemistry; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin D1 - metabolism; Cyclin E - metabolism; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophagus; Extracellular Signal-Regulated MAP Kinases - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatology; Humans; Medical sciences; Medicine; Medicine & Public Health; Niacinamide - analogs & derivatives; Oncology; Original Paper; Other diseases. Semiology; p38 Mitogen-Activated Protein Kinases - metabolism; Phenylurea Compounds; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-myc - metabolism; Pyridines - pharmacology; STAT3 Transcription Factor - metabolism; Transplant Surgery; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Barrett’s esophagus; Cyclin E; Cyclin D1; Sorafenib; Esophageal adenocarcinoma; Antineoplastic agent; Esophageal disease; Gastroenterology; Barrett's esophagus; Antiangiogenic agent; Tumor cell; Nutritional status; Human; Obesity; Premalignant lesion; Nutrition; Tyrosine kinase inhibitor; Nutrition disorder; Enzyme inhibitor; Metabolic diseases; Malignant tumor; Oesophageal adenocarcinoma; Digestive diseases; Esophagus adenocarcinoma; Multikinase inhibitor; Cancer
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-008-0294-y

Background and purpose Current therapies offer scant benefit to patients with advanced esophageal adenocarcinoma. We investigated the effects of Sorafenib, a multifunctional kinase inhibitor, on several growth regulatory pathways that control cell growth and survival in SEG-1 cells derived from Barrett’s adenocarcinoma. Methods SEG-1 cells were exposed to acidified medium or taurocholic acid, with and without pre-incubation with Sorafenib. Cyclin D1 and E, c-Myc, and Bcl-2 expression levels as well as STAT3 activations were determined by Western blotting. Cyclin D1 mRNA was measured by real-time PCR. Apoptosis was assessed by TUNEL assay. Results Sorafenib significantly inhibited SEG-1 cell proliferation stimulated by acid or bile acid treatments and reduced cell survival. This drug significantly reduced the up-regulations of cyclin D1, cyclin E, c-Myc, and Bcl-2 as well as the activation of STAT3 in SEG-1 cells. Conclusions These results support a rational basis for future clinical studies to assess the therapeutic benefit of Sorafenib in esophageal adenocarcinoma.